Dual phototherapy, including photodynamic therapy (PDT) and

photothermal therapy (PTT), is regarded as a more effective method for

cancer treatment than single PDT or PTT. However, development of single

component and near-infrared (NIR) triggered agents for efficient dual

phototherapy remains a challenge. Herein, a simple strategy to develop

dual-functional small-molecules-based photosensitizers for combined

PDT and PTT treatment is proposed through: 1) finely modulating

HOMO–LUMO energy levels to regulate the intersystem crossing (ISC)

process for effective singlet oxygen (1O2) generation for PDT; 2) effectively

inhibiting fluorescence via strong intramolecular charge transfer (ICT) to

maximize the conversion of photo energy to heat for PTT or ISC process

for PDT. An acceptor–donor–acceptor (A-D-A) structured small molecule

(CPDT) is designed and synthesized. The biocompatible nanoparticles,

FA-CNPs, prepared by encapsulating CPDT directly with a folate

functionalized amphipathic copolymer, present strong NIR absorption,

robust photostability, cancer cell targeting, high photothermal conversion

efficiency as well as efficient 1O2 generation under single 808 nm laser

irradiation. Furthermore, synergistic PDT and PTT effects of FA-CNPs

in vivo are demonstrated by significant inhibition of tumor growth. The

proposed strategy may provide a new approach to reasonably design and

develop safe and efficient photosensitizers for dual phototherapy against

cancer.